The research encompasses the development of "internal surface" reverse phase high performance packing supports for liquid chromatography. This new concept in HPLC packings, developed exclusively by the principal investigator, involves the production of reverse phase silica bonded supports to which the hydrophobic partitioning phase is bound only to the internal surface of the porous particulates. The pore diameter of the packing supports is small for complete exclusion of macromolecules and the external surface of the particulates is rendered hydrophilic so as to be non-adsorptive to human plasma proteins. The "internal surface" reverse phase liquid chromatographic supports are disigned to better facilitate the HPLC analysis of drugs in plasma. The new packing enables the direct injection of the plasma samples onto an HPLC system, thus completely eliminating conventional sample clean-up procedures.